Changing the shape of the fight against disease
Messenger RNA (also known as mRNA) molecules have attracted lots of attention in recent years as the foundation of the Pfizer and Moderna vaccines that unlock the body’s immune response to fight COVID-19.
Although they’ve been effective at preventing the virus, the VCU School of Pharmacy’s Guizhi (Julian) Zhu, Ph.D. notes mRNA molecules used in those vaccines still have room for improvement: their linear shape makes them more susceptible to being bro- ken down over time, he says.
“They’re easily degraded, and being easy to degrade can cause a lot of other problems,” explains Zhu, an assistant professor in the Department of Pharmaceutics. “The current CO- VID mRNA vaccines have to be frozen to prevent rapid degradation during storage and transportation. Also, when you get a COVID mRNA shot, you need to get another one in about six months. And that’s partially due to degradation.”
Zhu and Yu Zhang, Ph.D. are pursuing a project supported by VCU TechTransfer and Ventures seeking to improve on RNA immunotherapy technology by developing a method that instead produces the molecules with a circular shape. That makes them more durable, with a stronger immune response.
“By circularization, we make these molecules more stable so they’re not easily broken up,” Zhu says. “They can stay in the body and in a vial for a longer time and thus have a longer-lasting response.”
The approach may provide an im- proved way to make vaccines not just for COVID, but to combat the flu and prevent and treat various cancers like melanoma, breast cancer, brain cancer, and cancer caused by HPV infections.
Studies on mice show the circular RNA method is effective at launching a robust immune response and limiting the progression of tumors. This approach could also lead to a more cost- effective way to produce RNA vaccines and therapeutic treatments.
The research into the circular RNA project is supported by more than $3 million from the National Institutes of Health, the U.S. Department of Defense, and other sources.
TechTransfer and Ventures, meanwhile, contributed $50,000 to the research from its Commercialization Fund as well as the patenting, marketing, and licensing of the intellectual property. VCU Massey Cancer Center’s Molecule to Medicine program is also backing Zhu.
He says researchers are now working on attracting additional money, including investor funding, as they seek to take the project to human clinical trials initially as a cancer treatment. He notes VCU’s contribution to the research goes well beyond monetary support. “It’s the recognition,” Zhu says. “It’s the audience that they can bring us to.”